B Cells

B Cell Life Cycle

B cells develop in the bone marrow before completing maturation in the spleen. They may stay in the spleen or migrate to secondary lymphoid organs, where they become activated upon encountering an antigen.

Once activated, B cells undergo the germinal centre reaction, during which they proliferate and are selected with T-helper cell support – before differentiating into antibody-secreting plasma cells or memory B cells.

Created in BioRender

Fig 1
Overview of B cell life cycle

B Cell Development

B and T cells arise from common lymphoid progenitor cells within the bone marrow. Progenitor cells committed to the T cell lineage migrate to the thymus for maturation, whereas cells committed to the B cell lineage remain in the bone marrow.

Developing B cells express a B cell receptor (BCR), which is a membrane-bound immunoglobulin that allows antigen binding. B cells are then selected based on the properties of this receptor – ensuring that it is functional but not strongly self-reactive.

This selection process has two components:

• Positive selection – B cells with a functional BCR receive survival signals and continue development; those without a functional receptor undergo apoptosis.
• Negative selection – B cells with BCRs that bind strongly to self-antigens undergo receptor editing, functional inactivation (anergy), or apoptosis.

This process of selection produces immature B cells, which leave the bone marrow and migrate to the spleen to complete maturation as naïve (antigen-inexperienced) B cells.

B Cell Activation

Naïve B cells reside in lymphoid (B cell) follicles within the spleen or migrate to other secondary lymphoid organs such as lymph nodes and mucosal-associated lymphoid tissue.

This distribution allows immune surveillance of different compartments of the body:

• B cells in the spleen ‘screen’ for blood-borne antigens
• B cells in lymph nodes ‘screen’ for antigens in lymph draining from tissues
• B cells in the various MALTs ‘screen’ for antigens at mucosal surfaces

Naïve B cells become activated when they bind a foreign antigen via their BCR. Activated B cells form a germinal centre within the lymphoid follicle they reside in and present their antigen to a T-helper cell.

This enables B cells to undergo the germinal centre reaction, during which they proliferate and are selected with T-helper cell support. Following this process, they differentiate into antibody-secreting plasma cells or long-lived memory B cells.

Cenveo / CC-BY-3.0-US (http://creativecommons.org/licenses/by/3.0/us/)

Fig 2
Activated B cells receive help from a T-helper cell and differentiate into plasma or memory cells

T-Independent B Cell Activation

In most cases, B cells need to interact with T-helper cells for full activation. However, some antigens can activate B cells without T cell help and are termed T-independent antigens.

Some examples of T-independent antigens are the lipopolysaccharide (LPS) component of the cell wall of Gram-negative bacteria and the polysaccharide outer layer of encapsulated bacteria.

These antigens allow the associated bacteria to evade T cells but can still be recognised by B cells. B cells activated by T-independent antigens mainly produce IgM antibodies and do not generate memory B cells.

Plasma Cells

Plasma cells are large, terminally differentiated cells with abundant rough endoplasmic reticulum, allowing the production of large quantities of antibodies.

They arise following T cell–dependent B cell activation and secrete antibodies either transiently during infection or long term, particularly from the bone marrow. Plasma cells are often found in chronic inflammation.

Nephron / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)

Fig 3
Blood film showing a multinucleated plasma cell

Memory B Cells

Memory B cells are long-lived cells that remain within the body and allow a more rapid response to future infections as part of a secondary immune response.

If the host is re-exposed to the same antigen, these cells rapidly proliferate with assistance from T cells. This produces more cells capable of secreting specific antibodies to the pathogen.

As a result, the pathogen is often cleared before infection becomes established or symptomatic.